Study Questions:

Do the benefits of short-term dual antiplatelet therapy after minor stroke or transient ischemic attack (TIA) persist at 1 year?

Methods:

This study reports on the 1-year outcomes of the CHANCE (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events) trial. The CHANCE trial enrolled 5,170 Chinese patients after a minor stroke or TIA and randomized them to aspirin 75 mg daily plus clopidogrel 75 mg daily for 3 weeks, then clopidogrel 75 mg daily monotherapy for an additional 69 days or aspirin 75 mg daily for 90 days. Patients in the dual antiplatelet group had a lower risk of stroke (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.57-0.81; p < 0.001) at 90 days without an increased risk of bleeding. As there has been concern about rebound thrombotic events after stopping clopidogrel, the authors performed an additional visit at 1 year after enrollment, where they obtained information about antiplatelet agent use and outcome events (ischemic stroke, hemorrhagic stroke, myocardial infarction [MI], vascular death, and bleeding). Outcome events were assessed using the Cox proportional-hazards model. In both groups, after 90 days, the choice of antiplatelet treatment was at the discretion of the patient and physician.

Results:

Of the 5,170 enrolled subjects, there were 197 lost to follow-up at 1 year: 4.3% in the aspirin group and 3.3% in the clopidogrel group (p = 0.07). At 1 year, about 80% of the patients were on an antiplatelet agent, most commonly aspirin. There was no significant difference between the groups regarding the type of antiplatelet agent used (p = 0.55). Between 3 months and 1 year, 63 (2.7%) patients in the clopidogrel-aspirin group had a stroke compared with 59 (2.6%) in the aspirin group (HR, 0.96; 95% CI, 0.68-1.35; p = 0.81). At 1 year, there were fewer strokes (HR, 0.78; 95% CI, 0.65-0.93; p = 0.006), ischemic strokes (HR, 0.77; 95% CI, 0.64-0.93; p = 0.006), and stroke, MI, or vascular death (HR, 0.78; 95% CI, 0.65-0.93; p = 0.005) in the clopidogrel-aspirin group than the aspirin monotherapy group. There was no increased risk of bleeding in the clopidogrel-aspirin group (HR, 1.39; 95% CI, 0.95-2.04; p = 0.09).

Conclusions:

At 1 year, short-term dual antiplatelet therapy was associated with a decreased risk of stroke and vascular events.

Perspective:

In the CHANCE trial, short-term dual antiplatelet therapy reduced the risk of stroke at 3 months, but there was concern that longer-term outcomes would be impacted by rebound thrombotic events when clopidogrel was discontinued. This study, which looked at 1-year outcomes, showed that the transition from dual antiplatelet therapy to antiplatelet monotherapy (typically aspirin) was not associated with an increased risk of vascular events. In the 3-month to 1-year time frame, there was no significant difference in the rate of stroke between those initially randomized to clopidogrel plus aspirin versus aspirin alone. These results are encouraging, and an ongoing trial (POINT) will help to determine if they are generalizable to a Western, non-Chinese population.